This invention relates to compositions and methods for nutritional management of hepatic (liver) failure. In particular the invention is directed at novel amino acid compositions designed to meet the altered metabolic needs of patients suffering from hepatic failure and the attendant derangements of normal amino acid metabolism characterized by this clinical condition.
Hepatic failure has numerous potential causes. Included among these causes are traumatic injuries to the organ and metabolic causes of a chronic (e.g., alcoholism) or acute nature (e.g., hepatitis, sepsis).
Of the numerous functions performed by the liver, one in particular has importance as the subject of the invention described below. The liver is the site of detoxification of numerous substances, in particular those nitrogenous wastes associated with protein metabolism. Especially important is the toxic by-product, ammonia (NH.sub.3). The liver normally will detoxify ammonia by forming the nitrogen-containing substance urea (ureagenesis), which is then excreted via the kidneys.
When the liver is in various degrees of failure its ability to detoxify ammonia can become compromised. As a result ammonia can accumulate in the blood (hyperammonemia). It is a widely accepted belief among clinicians and researchers that hyperammonemia is dangerous, since ammonia is believed to be extremely toxic to the brain. A potential result of hyperammonemia is the onset or deepening of coma. When such coma is associated with hepatic failure it is termed "hepatic coma" or "hepatic encephalopathy".
Although the exact or immediate cause(s) of hepatic coma are not known with certainty, it is widely believed that ammonia can be a contributory factor. This is reflected in the fact that some of the non-nutritional therapeutic modalities employed in the clinical management of hepatic failure include treatments which have as their goal the reduction or elimination of ammonia input into the patient. Specifically, administration of the antibiotic, neomycin, and the synthetic carbohydrate, lactulose, are directed at reducing the production of ammonia by intestinal bacteria. It is known that the intestinal bacteria are the source of a substantial amount of ammonia, which reaches the blood-stream by intestinal absorption. Neomycin and lactulose are administered to reduce or eliminate this source of ammonia.
Current therapies for hepatic failure, with or without the complication of coma, are not generally nutritional in nature.
However, nutritional compositions which are disclosed to be tailored for hepatic failure are known. For example, see Ghadimi, U.S. Pat. No. 3,832,405, Fischer et al, U.S. Pat. No. 3,950,529 and West German Offenlegungsschrift 26 36 828.
It is known that certain amino acids (the L-forms of threonine, serine, tryptophan, glutamine, histidine, and glycine, hereafter termed "ammonotelic" amino acids) are catabolized by the body with the release of ammonia.
It is an object of this invention to supply an amino acid composition which will reduce the ammonia produced endogenously (by the body, rather than by bacterial floria) by reducing the proportion of ammonotelic amino acids present in the nutritional source.
It is another object to ameliorate the hyperammonemia which accompanies hepatic dysfunction, thereby reducing the likihood of a lapse into hepatic coma or a deepening of the comotase state.
It is an additional object to provide adequate nutrition to the hepatic diseased patient without compromising the foregoing two objects.
These and other objects will become apparent from the specification as a whole.